Study Evaluating Subjects With Distal Renal Tubular Acidosis

• ClinicalTrials.gov Identifier: NCT03644706
• Recruitment Status: Active, not recruiting
• First Posted: August 23, 2018
• Last Update Posted: April 28, 2020
• Sponsor: Advicenne Pharma
• Information provided by (Responsible Party): Advicenne Pharma

Study Description

Brief Summary:

This is a phase 3, prospective, multicenter, randomized, double-blinded, placebo-controlled, study product withdrawal study comparing the efficacy of ADV7103 versus placebo in preventing the development of metabolic acidosis defined by serum bicarbonate level in pediatric (6 months to < 18 years of age) and adult (18 to 65 years of age) subjects with primary dRTA.

Condition or disease	Intervention/treatment	Phase
Distal Renal Tubular Acidosis	Drug: ADV7103; Drug: Placebo	Phase 3

Detailed Description:

The study will target enrolling at least 4 subjects in each of the following age groups: 6 months - 23 months; 2-11 years, and ≥ 12 years. Subjects will be in the study for up to 21 weeks. After screening and enrollment, subjects will participate in an 8-12 week open label period where there dose of ADV7103 will be titrated to effect, then continued for the remainder of the open label period. Periodic measurements of bicarbonate and potassium levels will be collected during this period. Following the open-label period, subjects will enter a 6-day randomized withdrawal period. For this portion of the study, subjects will be admitted to an inpatient setting. A follow-up period up to four weeks on re-established therapy completes the trial. Subjects will have the opportunity to subsequently enter a long-term, open label extension.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 3 Multicenter, Randomized, Double-Blinded, Placebo-Controlled Withdrawal Study Evaluating ADV7103 In Pediatric and Adult Subjects With Distal Renal Tubular Acidosis (dRTA)
• Actual Study Start Date: January 31, 2019
• Estimated Primary Completion Date: February 1, 2021
• Estimated Study Completion Date: February 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: ADV7103; Patients continue to receive ADV7103 twice a day at their open label dose over 6 days	Drug: ADV7103; Each dose of ADV7103 contains a fixed ratio of 1/3 of ADV7103-CK (potassium citrate) and 2/3 of ADV7103-BK (potassium bicarbonate) based on the mass of active substances. The strength is 6.44 (± 10 %) mEq/g of ADV7103 (alkalinizing power).; Other Name: Potassium Citrate and Potassium Bicarbonate
Placebo Comparator: Placebo Comparator; Patients receive matched placebo twice a day until they reach a bicarbonate level of 18mEq/L	Drug: Placebo; Placebo is a combination of 2 mm green coated lactose granules and 2 mm white coated lactose granules. Each dose of placebo contains a fixed ratio of 1/3 of green granules and 2/3 of white granules.

Outcome Measures

Primary Outcome Measures :

1. Mean change in blood bicarbonate levels [ Time Frame: 6 days ]
   Compare the efficacy of ADV7103 versus placebo in preventing metabolic acidosis, defined as 2 consecutive serum bicarbonate levels < 18 mEq/L for subjects ≥ 4 years old and < 17 mEq/L for subjects < 4 years old, during the Withdrawal Period

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Female or male subjects ≥ 6 months of age and ≤ 65 years of age at time of consent;
2. Subject presents with a previous diagnosis of primary dRTA of at least 4 months duration for subjects < 12 years of age, and at least one year for those ≥ 12 years of age, based on documented history of non-anion gap, hyperchloremic, hypokalemic metabolic acidosis;
3. Subject requires ≥ 0.9 mEq/kg/day of alkali therapy to maintain serum bicarbonate levels above the LLN for the laboratory providing results;

Exclusion Criteria:

1. Female subject who is pregnant or lactating or has plans for pregnancy during the study;
2. Subject has evidence of proximal tubule dysfunction (eg, hypophosphatemia, low serum uric acid, glycosuria, or amino aciduria);
3. Subject presents with another diagnosed condition as a potential etiology for her/his dRTA (eg, systemic lupus erythematosus, Sjogren's syndrome), in the opinion of the Investigator;
4. Subject requires therapy with potassium sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, trimethoprim, drospirenone and other progestins, nephrotoxic antibiotics, penicillins, tacrolimus, or medications known to delay gastric emptying or otherwise interfere with absorption of study product;
5. Subject has evidence of obstructive uropathy or other findings on renal ultrasound associated with Visit 1 expected to require intervention during the course of the study, in the opinion of the Investigator;

6. Subject has any of the following laboratory abnormalities associated with Visit 1:

   1. AST and/or ALT > 1.5x upper limit of normal (ULN)
   2. Serum potassium > 5.0 mEq/L or hypokalemia accompanied by clinical symptoms (eg, muscle cramps) or significant ECG changes (eg T wave depression, U wave elevation)
   3. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (according to the updated Schwartz formula for children and Chronic Kidney Disease - Epidemiology Collaboration [CKD-EPI] formula for adults)
   4. Total bilirubin > ULN, except with known Gilbert's disease.
7. Subject has been hospitalized or had outpatient surgery (other than minor skin and dRTA disease-related procedures or ear tube placement) in the past 6 months or is planning surgery in the next 6 months;

Contacts and Locations

Locations

United States, California

University of California

San Francisco, California, United States, 94158

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, Connecticut

Connecticut Children's Hospital

Hartford, Connecticut, United States, 06106

United States, Florida

University of South Florida Pediatric Infectious Disease

Tampa, Florida, United States, 33606

United States, Georgia

Emory Children's Center

Atlanta, Georgia, United States, 30322

United States, Indiana

J.W. Riley Hospital for Children

Indianapolis, Indiana, United States, 46202

United States, Missouri

Washington University/St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

United States, Pennsylvania

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Canada, Alberta

University of Alberta

Edmonton, Alberta, Canada, T6G 2R3

Canada, Ontario

The Hospital for Sick Children

Toronto, Ontario, Canada, M5G 1X8

Canada, Quebec

The Research Institute of the McGill University Health Centre

Montreal, Quebec, Canada, H4A 3J1

Sponsors and Collaborators

Advicenne Pharma

Investigators

• Study Chair: Andre Ulmann, MD, Ph.D.; Advicenne Pharma

More Information

Additional Information:

Patient information regarding the disease under study and protocol information 

Patient education 

Company website 

• Responsible Party: Advicenne Pharma
• ClinicalTrials.gov Identifier: NCT03644706
• Other Study ID Numbers: B23CS
• First Posted: August 23, 2018
• Last Update Posted: April 28, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Acidosis, Renal Tubular; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Potassium Citrate; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Expectorants; Respiratory System Agents